Radiation therapy is one of the main treatment methods for cancer. Machine learning can be used in all aspects of clinical practice in radiation therapy, including clinical decision support, automatic segmentation of target volumes, prediction of treatment efficacy and side effects. Despite the challenges of lacking structured data and poor interpretability of models, the application of machine learning in radiotherapy will become increasingly profound and extensive. This review contains three aspects: introduction of machine learning, the clinical application of machine learning in radiotherapy, challenges and solutions.

Objectiye To study the levels of cartilage oligomeric matrixprotein (COMP) and matrix metalloproteinase-3 (MMP-3) in the serum fluid of osteoarthritic rabbit models and their relationships with the severity of pathological changes, so as to investigate their correlation with osteoarthritis(OA). Methods The osteoarthritic animal models were get from immobilizing the right knees of 18 rabbits in full extension using plaster cast. Knee joint pathological changes of 2,6 weeks were examined for pathological severity of OA; ELISA sandwich method was used to measure the levels of COMP and MMP-3 in serum before and after modeling( at 2, 6 weeks respectively); X ray of model keens was also obtained in different period.Correlation analysis was performed to demonstrate the relationship between the levels of COMP, MMP-3 in the serum and the pathological severity of OA. Results ( 1 ) Morphological observations: immobilizing the right knees of rabbits in full extension using plaster cast was a reliable methed for osteoarthritic animal models and the typical histopathologic character was seen; the severity of osteoarthritisgradually increased with time extended. (2) The levels of COMP[(3.64 ±0. 18)μg/L], MMP-3 [(1.99 ±0. 81 ) μg/L]in the serum of 2 weeks osteoarthritic animal models were higher than those before immobilizing with plaster cast [COMP(3.35 ±0. 20) μg/L,MMP-3( 1.61 ±0. 71 ) μg/L]. The levels of COMP[(3.96 ±0. 44) μg/L],MMP-3[(3.44 ±0. 91) μg/L] of 6 weeks were much higher,with a significant difference(P ＜0.05). The levels of COMP, MMP-3 in serum had a linear correlation with the pathological severity of OA (r ＞0. 710,and P ＜ 0. 05 ). Conclusion The levels of COMP and MMP-3 in serum can help to predict and evaluate the progression of OA.

Objective To study the diagnostic value of cartilage oligomeric matrix protein for early cartilage destruction in osteoarthritis and assess its value in the prediction of the disease progression.Methods The osteoarthritis animal models were developed by immobilizing the right knees of 18 rabbits in full extension position using plaster East.Knee joint pathological changes at week 2 and 6 were examined for pathological severity evaluation of osteoarthritis.ELISA sandwich method was used to measure the levels of cartilage oligomeric matrix protein(COMP) in serum before and after modeling(at week 2 and 6 respectively) and immunohistolgy method was used to examine the levels of COMP in knee articular cartilage of osteoarthritis animal models.Correlation analysis was performed to demonstrate the relationship between the levels of COMP in the serum and the pathological severity of osteoarthritis.Pearson's test and t-test were used for correlation analysis.Results ①) Osteoarthritis animal models could be successfully developed by immobilizing the right knees of rabbits in full extension position using plaster east for 2 weeks.Early histopathological changes in the articular cartilage could be observed,At week 6,the typical histopathological characteristics could be seen.②With the extension of modeling time,serum COMP levels persistently increased.The serum COMP levels before modeling,at modeling week 2,week 6 were (3.35±0.20),(3.64±0.18),(3.96±0.44) μg/L respectively,the difference was significant (P＜0.05).③ The level of COMP in the articular cartilage of non-osteoarthritis animal models,models at week 2,week 6 were (2.7±1.8 )％ ,(5.7±0.7)％,(7.6±0.7)％ respectively (P＜0.05 for all).④ The level of COMP in the serum was linearily correlated with the pathological severity of osteoarthritis(r＞0.770 for all,and P＜0.05 for all).Conclusion Levels of COMP in the serum can help to make early diagnosis of osteoarthritis,and elevated COMP level can predict the progression of osteoarthritis.

Objective To evaluate the plan quality of volumetric modulated arc therapy (VMAT) in single brain metastasis compared with the stereotactic arc therapy (S_ARC).Methods 31 patients were replanned using VMAT and S_ARC technique.Prescription dose is 40 Gy delivered in 4 fractions covering at least 95％ of the target volume while keeping minimum doses to the volume of normal brain tissue.The plans were assessed and compared using the conformity indexes (CI),gradient indexes (GI),the mean dose of normal brain tissue,the volumes of normal brain tissue receiving 4 Gy doses,the number of monitor unit and treatment times.A paired t test or non-parametric Wilcoxon signed rank test was performed to analyze the difference between these two plans.Results VMAT plans increased dose conformity,but not dose gradient,compared with S_ARC plans.The median dose conformity index values were 0.815,0.818,and 0.779 (P =0.000,0.000),and the median dose gradient score index values were 5.865,5.706,and 3.133(P =0.000,0.000,0.000),in single arc,double arc VMAT plans and S_ARC plans,respectively.The mean dose of normal brain tissue was higher in VMAT plans.And the volume of the normal brain tissue receiving doses of 4 Gy in VMAT plans was significantly larger than the volume in S_ARC plans.The VMAT plans got higher MU number (P =0.000,0.000).And the mean treatment times were (2.7 ± 0.1) min,(2.8 ± 0.1) min,and (7.6 ± 0.2) min in single arc,double arc VMAT plans and S_ ARC plans,respectively (P =0.000,0.000).Conclusions The dosimetry of VMAT plan can meet the requirements of clinical,and is recommended in the treatment of big volume single brain metastasis or single brain metastasis in cerebellum.

Objective To evaluate effectiveness of the applying pelvic double-slice retractor in the division of bladder and prostate pedicles in male patients with previous surgery history during radical cystectomy (RC) and anterograde radical prostatectomy (ARP). Methods The pelvic double-slice retractor was used to expose the bladder and prostate pedicles in 43 RC (30 cases with BMI ＞ 28 kg/m2,16 cases had previous partial cystectomy) and 37 ARP ( all cases with BMI ＞ 28 kg/m2 ). Results The pelvic double-slice retractor provided excellent exposure for the division of bladder and prostate pedicles.The handling of bladder and prostate pedicles became easy and safe without unnecessary bleeding and injury to the rectum.The median operating time to control the pedicles during RC and ARP were 12 min and 7 min,and the average blood loss were 30 ml and 20 ml,respectively. Conclusion The use of pelvic double-slice retractor for the exposure of the bladder and prostate pedicles is simple and effective in male patients with complicated pelvic anatomy during RC and ARP.

Objective　To find out if an unique blood mode-vasculogenic mimicry (VM) exist in prostate cancer and analyze its relationship with prognosis.　Methods　The age of the patients was 59 to 72 years,with a mean age of (66.7 ± 11.0) years.All had been confirmed as prostate cancer by biopsy.The level of serum PSA was 15.6 to 76.7 μg/L,with a mean level of (34.6 ± 1.7 ) μg/L.A histochemical and immunohistochemical dual staining method for PAS-CD31 and MMP-2 in 96 prostatic adenocarcinomas were conducted to explore if VM exist in prostate cancer,describe its morphology and distribution.The different expression of MMP-2 in VM positive and VM negative tissue were.The clinical data were collected and analyzed to explore the relationship between disease progression and VM.　Results　Among 96 cases,24 cases were found VM positive,the others were negative.The boundary membrane of VM was PAS positive,which was continuous or incontinuous. A positive correlation between VM density and high Gleason score were found.The tPSA were higher in the VM positive cases than that in VM negatives.The VM positive patients had poorer prognosis than that of the negatives.The MMP-2 expression was found correlated with VM positive (rs =0.60,P ＜ 0.01 ).　Conclusions　VM exists in the prostate cancer as an independent structure,and it is more common in the high-grade cancer.The progression-free survival of VM positive patients could be worse than the negative.MMP-2 and VM could be the indicators of poor prognosis.

Objective To evaluate the effects of four types of variance reduction techniques ( ring counter grid, high electron cutoff energy, termination of electron tracking in some structures, and emission direction?biased sampling of source) on the efficiency and accuracy of Monte Carlo simulation for the single source channel of the Leksell Gamma Knife. Methods The single source channel of the Leksell Gamma Knife was modeled using Monte Carlo software MCNP . Four types of variance reduction techniques were used to simulate the dose distribution in the water?like phantom. The computation efficiency and simulation result were compared between the four techniques. Results All techniques substantially improved the computation efficiency and had little effect on the accuracy of the simulation ( relative error less than 2. 5%) . However, if the electron cutoff energy was above 50 keV, the simulation became quite inaccurate due to neglect of the scattering of high?energy electrons and their dosimetric contribution to the penumbra. When the scattering of high?energy electrons and their dosimetric contribution to the penumbra were ignored, the dose to the Profile platform was overestimated and the dose to the penumbra was underestimated. Conclusions Rational use of variance reduction techniques can substantially improve the efficiency of Monte Carlo simulation for the single source channel of the Leksell Gamma Knife. However, the impact of variance reduction techniques on the accuracy of the simulation should be carefully evaluated.

Objective To develop whole breast irradiation with volumetric-modulated arc therapy (VMAT)-based hybrid intensity-modulated radiotherapy (IMRT) after breast conserving surgery for breast cancer,and to evaluate its value in clinical application.Methods Ten patients with breast cancer undergoing breast conserving surgery were enrolled.Two radiotherapy plans were designed based on hybrid fixed-beam IMRT/IMRT technique and hybrid VMAT/IMRT technique,respectively.One group received whole breast irradiation with a prescribed dose of 50 Gy in 25 fractions.The other group received whole breast irradiation with a prescribed dose of 50 Gy in 25 fractions,as well as simultaneous integrated boost to the tumor bed with 60 Gy in 25 fractions.The dosimetric parameters and delivery efficiency were compared between the two plans using paired t test.Results For patients treated with whole breast irradiation alone,there were no significant differences in conformity index and homogeneity index of target volume between the two plans (P=0.866,0.056);however,compared with the hybrid fixed-beam IMRT/IMRT technique,the hybrid VMAT/IMRT technique significantly increased the doses to organs at risk (OARs) and the number of monitor units (MUs) in the intensity-modulated field (P=0.000-0.050,P=0.002).For patients treated with whole breast irradiation with a simultaneous integrated boost to the tumor bed;however,the hybrid VMAT/IMRT technique significantly reduced the doses to the lung and spinal cord,number of MUs in intensity-modulated field,and delivery time compared with the hybrid fixed-beam IMRT/IMRT technique (P=0.004,0.001,0.000,0.000).Conclusions For patients treated with whole breast irradiation with a simultaneous integrated boost to the tumor bed,the hybrid VMAT/IMRT technique is highly promising for clinical application due to better OAR sparing and higher delivery efficiency.

Objective To evaluate the application value of inhibitor enhanced modified carbapenemase inactivation method (imCIM) in the detection of class B carbapenemase.The differences between imCIM and EDTA disc potentiation test (EDPT) were comparatively analyzed.Methods A total of 181 strains of carbapenem insensitive strains were collected,among which there were 44 strains of Klebsiella pneumoniae,44 strains of Escherichia coli,43 strains of Acinetobacter baumannii and 50 strains of Pseudomonas aeruginosa.The 83 strains of carbapenem-sensitive strains were composed of 25 strains of Klebsiella pneumoniae,16 strains of Escherichia coli,25 strains of Acinetobacter baumannii and 17 strains of Pseudomonas aeruginosa.The class B carbapenemase in the 264 strains of pathogenic bacteria was screened by imCIM and EDPT,and PCR results were used as gold standard.The statistical analysis wasperformed with consistency check,related-sample Wilcoxon signed rank sum test,independent samples Kruskal-Wallis H test and ROC curve.Results Among the 181 strains of carbapenem insensitive strains,PCR results of 144 strains were positive for drug resistance gene.The samples of class A,B and D of carbapenemase were 39,77 and 28 strains respectively.The results of imCIM showed that 70 strains were positive,and the other 111 strains were negative.The imCIM results of 166 strains were consistent with those of PCR.The results of EDPT showed that 72 strains were positive,and the other 109 strains were negative.The EDPT results of 134 strains were consistent with those of PCR.The results of PCR,EDPT and imCIM of 83 carbapenem sensitive strains were negative.The sensitivity and specificity of imCIM were 85.71％ (66/77) and 97.86％ (183/187),and the value of Kappa was 0.859.The sensitivity and specificity of EDPT were 66.23 ％ (51/77) and 88.77 ％ (166/187),and the value of Kappa was 0.561.The difference of inhibition zone of imCIM (AdimCIM) was different from EDPT(AdEDPr) and the difference was statistically significant (Z =-6.941,P ＜ 0.05).In the imCIM detection,the AdimciM level of class B carbapenemase showed different population distribution position from class A and D carbapenemase with the statistically significant difference (x2 =108.887,P ＜ 0.05).The areas under the ROC curve of imCIM and EDPTwere 0.988 (95％CI:0.977 to0.999) and0.936 (95％CI:0.909 to0.963),respectively.Conclusion imCIM should be accurate,efficient and convenient for screening of carbapenem phenotype for its high sensitivity and specificity,and suitable for epidemiological monitoring.

Objective To investigate the feasibility of modified rapid Carba NP test for the detection of carbapenemase,and analyze the differences between the modified method and Carba NP test.Methods A total of 264 strains of gram-negative bacillus,including 164 carbapenem-resistant strains and 100 sensitive strains,were collected,and their carbapenemase were detected by Carba NP test and the modified rapid Carba NP test,respectively.The differences between the two tests were evaluated based on PCR as a reference.Results Among 164 carbapenem-resistant strains,carbapenemase gene was detected in 144 strains by PCR.The carbapenemase gene was negative in 100 sensitive strains.Among 164 carbapenem-resistant strains,135 were positive for the Carba NP test,while 130 for the modified rapid Carba NP test.One hundred of sensitive strains were negative for the two Carba NP tests.Compared with the results of PCR,the sensitivity,specificity and Kappa value of the Carba NP test were 91.7％ (132/144),97.5％ (117/120) and 0.886,respectively,while those of the modified rapid Carba NP test were 89.6％ (129/144),99.2％ (119/120) and 0.879,respectively.There was no significant difference in the positive rates between Carba NP test and the modified rapid Carba NP test (x2 =1.45,P ＞ 0.05).Conclusion The modified rapid Carba NP test which has high consistency with the PCR method,is faster and cheaper than the Carba NP test,and may be applied to epidemiologic survey and the early monitoring of nosocomial infections.